The objectives of this collaborative effort are to characterize chemically and functionally the putative chemical mediators of immediate type hypersensitivity reactions. Certain of the recognized mediators such as slow reacting substance of anaphylaxis (SRS-A), the intermediate molecular weight eosinophilotactic peptides, and the structural analogs of the tetrapeptides of the eosinophil chemotactic factor of anaphylaxis (ECF-A) will be further characterized and provided in amounts sufficient for in vitro and in vivo analyses of their effects in animal model or human pulmonary tissue systems. The neutral peptide, a product of the interaction of an alpha-1-antitrypsin sensitive neutrophil ectoprotease and a plasma protein substrate, and the solubilized purified ectoprotease itself will also be provided in purified form in amounts sufficient for study of their respective actions on pulmonary tissues in model in vitro animal and human systems and in vivo animal models. A number of interrelated approaches will be used to define the relationships between the pathophysiology and immunology of various aspects of asthma and to then determine how these aspects relate to the overall diathesis. These include the further clarification and definition of the effects of chemical mediators of defined structure alone, and in combination, on normal and asthmatic airways, and the characterization of the airway response to various stimuli to which asthmatics are frequently exposed in their environment, such as exercise, specific antigen, and aspirin. In addition to physiologic assessments, mediator release kinetics will also be sought in the peripheral circulation.